MM2-type sporadic Creutzfeldt-Jakob disease: new diagnostic criteria for MM2-cortical type

2020 ◽  
Vol 91 (11) ◽  
pp. 1158-1165
Author(s):  
Tsuyoshi Hamaguchi ◽  
Nobuo Sanjo ◽  
Ryusuke Ae ◽  
Yosikazu Nakamura ◽  
Kenji Sakai ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Sensitivity And Specificity ◽  
Disease Surveillance ◽  
Early Stage ◽  
Prion Diseases ◽  
Brain Mri ◽  
High Sensitivity ◽  
Diffusion Weighted Images ◽  
Jakob Disease ◽  
New Criteria

ObjectiveTo clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity and specificity.MethodsWe reviewed the results of Creutzfeldt-Jakob disease Surveillance Study in Japan between April 1999 and September 2019, which included 254 patients with pathologically confirmed prion diseases, including 9 with MM2C-type sCJD (MM2C-sCJD) and 10 with MM2T-type sCJD (MM2T-sCJD), and 607 with non-prion diseases.ResultsAccording to the conventional criteria of sCJD, 4 of 9 patients with MM2C- and 7 of 10 patients with MM2T-sCJD could not be diagnosed with probable sCJD until their death. Compared with other types of sCJD, patients with MM2C-sCJD showed slower progression of the disease and cortical distribution of hyperintensity lesions on diffusion-weighted images of brain MRI. Patients with MM2T-sCJD also showed relatively slow progression and negative results for most of currently established investigations for diagnosis of sCJD. To clinically diagnose MM2C-sCJD, we propose the new criteria; diagnostic sensitivity and specificity to distinguish ‘probable’ MM2C-sCJD from other subtypes of sCJD, genetic or acquired prion diseases and non-prion disease controls were 77.8% and 98.5%, respectively. As for MM2T-sCJD, clinical and laboratory features are not characterised enough to develop its diagnostic criteria.ConclusionsMM2C-sCJD can be diagnosed at earlier stage using the new criteria with high sensitivity and specificity, although it is still difficult to diagnose MM2T-sCJD clinically.

scholarly journals Diagnosis of prion diseases by RT-QuIC results in improved surveillance

Neurology ◽  
2020 ◽  
Vol 95 (8) ◽  
pp. e1017-e1026 ◽  
Author(s):  
Daniel D. Rhoads ◽  
Aleksandra Wrona ◽  
Aaron Foutz ◽  
Janis Blevins ◽  
Kathleen Glisic ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Prion Disease ◽  
Disease Surveillance ◽  
Prion Diseases ◽  
False Negative ◽  
High Sensitivity ◽  
Disease Type ◽  
Diagnostic Sensitivity ◽  
Class Iii ◽  
The Impact

ObjectiveTo present the National Prion Disease Pathology Surveillance Center's (NPDPSC’s) experience using CSF real-time quaking-induced conversion (RT-QuIC) as a diagnostic test, to examine factors associated with false-negative RT-QuIC results, and to investigate the impact of RT-QuICs on prion disease surveillance.MethodsBetween May 2015 and April 2018, the NPDPSC received 10,498 CSF specimens that were included in the study. Sensitivity and specificity analyses were performed on 567 autopsy-verified cases. Prion disease type, demographic characteristics, specimen color, and time variables were examined for association with RT-QuIC results. The effect of including positive RT-QuIC cases in prion disease surveillance was examined.ResultsThe diagnostic sensitivity and specificity of RT-QuIC across all prion diseases were 90.3% and 98.5%, respectively. Diagnostic sensitivity was lower for fatal familial insomnia, Gerstmann-Sträussler-Scheinker disease, sporadic fatal insomnia, variably protease sensitive prionopathy, and the VV1 and MM2 subtypes of sporadic Creutzfeldt-Jakob disease. Individuals with prion disease and negative RT-QuIC results were younger and had lower tau levels and nonelevated 14-3-3 levels compared to RT-QuIC–positive cases. Sensitivity was high throughout the disease course. Some cases that initially tested RT-QuIC negative had a subsequent specimen test positive. Including positive RT-QuIC cases in surveillance statistics increased laboratory-based case ascertainment of prion disease by 90% over autopsy alone.ConclusionsRT-QuIC has high sensitivity and specificity for diagnosing prion diseases. Sensitivity limitations are associated with prion disease type, age, and related CSF diagnostic results. RT-QuIC greatly improves laboratory-based prion disease ascertainment for surveillance purposes.Classification of evidenceThis study provides Class III evidence that second-generation RT-QuIC identifies prion disease with a sensitivity of 90.3% and specificity of 98.5% among patients being screened for these diseases due to concerning symptoms.

scholarly journals Creutzfeldt–Jakob disease surveillance in Australia: update to December 2017

2019 ◽  
Vol 43 ◽  
Author(s):  
Christiane Stehmann ◽  
Shannon Sarros ◽  
Matteo Senesi ◽  
Victoria Lewis ◽  
Marion Simpson ◽  
...  
Keyword(s):  
Prion Disease ◽  
Disease Surveillance ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Annual Number ◽  
Prospective Surveillance ◽  
Surveillance Period ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
Neuropathological Examination

Nationwide surveillance of human prion diseases (also known as transmissible spongiform encephalopathies), the most common being Creutzfeldt–Jakob disease (CJD), is performed by the Australian National Creutzfeldt–Jakob Disease Registry (ANCJDR), based at the University of Melbourne. National surveillance encompasses the period since 1970, with prospective surveillance occurring from 1993 onwards. Over this prospective surveillance period considerable developments have occurred, especially in relation to pre-mortem diagnostics, the delineation of new disease subtypes and a heightened awareness of prion diseases in the health care setting. The surveillance practices of the ANCJDR have evolved and adapted accordingly. Since the ANCJDR began offering cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased to a maximum of 508 in 2017. The number of CSF test referrals in 2017 represents a 20% increase compared to that of 2016. In 2017, there was an overall stabilisation of the annual incidence rate of confirmed prion disease in Australia at expected levels; 72 persons with suspected human prion disease were added to the national register, with 72% of all suspected CJD cases undergoing neuropathological examination. The majority of the 72 suspected cases added to the register are as of 31 December 2017 still classified as “incomplete” (47 cases), while four cases were excluded by either detailed clinical follow-up (1 case) or neuropathological examination (3 cases); 19 cases were classified as definite and two as probable prion disease. No cases of variant CJD (vCJD) were confirmed.

scholarly journals Cardiomyopathy associated with Ceutzfeld–Jakob disease: a diagnosis of exclusion: a case report

2020 ◽  
Vol 4 (1) ◽  
pp. 1-5
Author(s):  
Osnat Itzhaki Ben Zadok ◽  
Katia Orvin ◽  
Edna Inbar ◽  
Eldad Rechavia
Keyword(s):  
Safety Concern ◽  
Brain Mri ◽  
Prnp Gene ◽  
Mortality Data ◽  
High Signal ◽  
Spongiform Encephalopathy ◽  
Diffusion Weighted Images ◽  
Jakob Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Work Up

Abstract Background Creutzfeldt–Jakob disease (CJD), the most common prion disease in humans, is primarily known for its adverse neurological impact and inevitable mortality. Data regarding myocardial involvement in CJD are scarce. Case summary A 54-year-old female patient, presented with progressive effort dyspnoea, was diagnosed with unexplained non-ischaemic cardiomyopathy. An extensive cardiac work-up including cardiac magnetic resonance imaging (MRI) did not reveal any underlying aetiology. Simultaneously, the patient developed involuntary limb movements and progressive cognitive decline. Thalamic high-signal abnormalities on diffusion-weighted images were apparent on brain MRI. Based on these findings, she was subsequently referred to a neurology department, where she suddenly died the day after her admission. Brain autopsy demonstrated spongiform encephalopathy. A genetic analysis performed to her son revealed a mutation in the PRNP gene; all of these were consistent with CJD. Discussion This case describes the clinical association of CJD and cardiomyopathy and the diagnosis prion-induced cardiomyopathy by exclusion. It is not inconceivable that the coexistence of these two clinical entities may be related to genetic expression and contemporaneously deposition of infectious prions in myocardial muscle and brain tissue. Awareness of this possible association could be of important public-safety concern, and merits further collaborative cardiac-neurological work-up to elucidate this phenotype among patients with unexplained cardiomyopathy with neurological symptoms that resemble CJD.

Blood-based detection of early-stage colorectal cancer using multiomics and machine learning.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 66-66
Author(s):  
Girish Putcha ◽  
Tzu-Yu Liu ◽  
Eric Ariazi ◽  
Marvin Bertin ◽  
Adam Drake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Machine Learning ◽  
Sensitivity And Specificity ◽  
Late Stage ◽  
Early Stage ◽  
High Sensitivity ◽  
Average Risk ◽  
Learning Platform ◽  
Pathological Subtypes ◽  
Mean Sensitivity

66 Background: Despite population screening efforts, screening rates for colorectal cancer (CRC) remain suboptimal. A non-invasive, blood-based screening test with high sensitivity and specificity in early-stage disease should improve adherence and ultimately reduce mortality; however, tests based only on tumor-derived biomarkers have limited sensitivity. Here we used a multiomic, machine learning platform to discover, refine, and combine tumor- and immune-derived signals to develop a blood test for the detection of early-stage CRC. Methods: Samples from 591 participants enrolled in a prospective study including average-risk screening and case-control cohorts (NCT03688906) were included in this analysis (CRC: n = 43; colonoscopy-confirmed CRC-negative controls: n = 548). Participants with CRC were 60% male with a mean age of 63, and controls were 55% male with a mean age of 60. Stage distribution was 54% early (I/II) and 34% late (III/IV) with 11% unknown. Plasma was analyzed by whole-genome sequencing, bisulfite sequencing, and protein quantification methods. Computational methods were used to assess and infer the performance of individual and combined assays. Results: For colorectal adenocarcinoma, which represents ~95% of all CRCs, our multiomic test achieved a mean sensitivity of 92% in early stage (n = 17) and 84% in late stage (n = 11) at a specificity of 90%. Across all CRC pathological subtypes, our test achieved a mean sensitivity of 80% in early stage (n = 19) and 83% in late stage (n = 12) at a specificity of 90%; the test detected the single squamous cell carcinoma but missed both neuroendocrine tumors. Individual assays achieved a mean sensitivity of 50% in early stage and 66% in late stage at a specificity of 90%. Conclusions: In a prospective cohort, we demonstrated high sensitivity and specificity for early-stage adenocarcinoma by combining tumor- and immune-derived signals from cfDNA, epigenetic, and protein biomarkers. While most CRCs are adenocarcinomas, detection of all pathological subtypes is required to maximize sensitivity in a screening population. Further analysis of molecular and pathological subtypes, as well as the entire ~3000 patient cohort, is underway. Clinical trial information: NCT03688906.

The utility of six serum tumor markers in early detection of lung cancer

2019 ◽  
Author(s):  
Qingwen Jiang ◽  
Xu Zheng ◽  
Yiting Li ◽  
Weina Huang ◽  
Xinjian Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Sensitivity And Specificity ◽  
Operating Characteristic ◽  
Early Stage ◽  
High Sensitivity ◽  
Roc Curves ◽  
Serum Levels ◽  
Benign Diseases ◽  
Significant Difference ◽  
Diagnosis Of Lung Cancer

Abstract Background: Lung cancer has become the leading cause of cancer-related death in China. However, most of patients were diagnosed at advanced stage. Thus, novel lung cancer diagnostic tests, which can be used to screen individuals in early stage, are required.Methods: A total of 208 patients involving 161 cases of lung cancer and 47 cases of benign diseases were enrolled. Serum concentration of GTM, CETM, PTM, CTM, ETM and HTM were analyzed by kits according to the manufacturer’s guidelines.Results: The results showed significant difference in serum concentrations of GTM, CETM, PTM, CTM, ETM, and HTM between patients with lung cancer and benign diseases. In addition, when compared with benign diseases, higher levels of those six markers were also observed in patient with SCC and SCLC, but not for ADC. Receiver operating characteristic (ROC) curves were further suggested a high sensitivity and specificity of six markers to identify lung cancer.Conclusion: The serum levels of GTM, CETM, PTM, CTM, ETM and HTM in lung cancer were significantly higher than those of benign diseases. Moreover, these six biomarkers showed a high sensitivity and specificity to identify a patient with malignant. These findings suggested that detection of those six biomarkers in serum might be helpful for differential diagnosis of lung cancer.

scholarly journals Prominent Prolongation of Cortical Silent Period Induced by Transcranial Magnetic Stimulation in Creutzfeldt-Jakob Disease

2020 ◽  
Vol 12 (3) ◽  
pp. 447-451
Author(s):  
Hideyuki Matsumoto ◽  
Naohiro Uchio ◽  
Akihito Hao ◽  
Mari Haga ◽  
Chiaki Abe ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Early Stage ◽  
Brain Magnetic Resonance Imaging ◽  
Silent Period ◽  
Progressive Dementia ◽  
Cortical Silent Period ◽  
Diffusion Weighted Images ◽  
Jakob Disease ◽  
Early Biomarker

The cortical silent period (CSP) induced by transcranial magnetic stimulation (TMS) has been reported to be prolonged in 2 Creutzfeldt-Jakob disease (CJD) patients who presented with periodic myoclonus. Herein, we will show a prominent prolongation of TMS-induced CSP in a patient with CJD who did not have periodic myoclonus. The patient was a 66-year-old woman who developed rapidly progressive dementia. No myoclonic jerks were observed. Brain magnetic resonance imaging showed high-intensity lesions in the cerebral cortex, basal ganglia, and thalamus on diffusion-weighted images. Electroencephalography (EEG) showed diffuse and continuous slow waves, but no periodic synchronous discharges (PSDs). A TMS study revealed that the duration of CSP was prominently prolonged: the duration of CSP (370 ms) equaled that of the mean + 6.5 SD of the normal value. One month after admission, the patient exhibited akinetic mutism and developed periodic myoclonus in her limbs. The clinical course was compatible with CJD. To date, CSP has been measured in only 2 CJD patients. The common findings in both cases were marked prolongation of CSP, periodic myoclonus, and PSD on EEG. In short, we demonstrated that TMS-induced CSP was prominently prolonged even at the early stage of CJD without periodic myoclonus or PSD. In other disorders, the CSP has not been reported to be comparably prolonged to that of CJD patients. Therefore, we conclude that TMS-induced CSP could be prominently prolonged even in the early stage of CJD. The marked prolongation of the CSP might be an early biomarker of CJD.

Explicit Diagnostic Criteria for Transient Ischemic Attacks Used in the Emergency Department Are Highly Sensitive and Specific

2020 ◽  
pp. 1-6
Author(s):  
Carl H. Göbel ◽  
Sarah C. Karstedt ◽  
Thomas F. Münte ◽  
Hartmut Göbel ◽  
Sebastian Wolfrum ◽  
...  
Keyword(s):  
Emergency Department ◽  
Diagnostic Criteria ◽  
Sensitivity And Specificity ◽  
Clinical Symptoms ◽  
Correct Diagnosis ◽  
Tertiary Care ◽  
High Sensitivity ◽  
University Hospital ◽  
Care Hospital ◽  
Transient Ischemic Attacks

<b><i>Background:</i></b> Making a correct diagnosis of a transient ischemic attack (TIA) is prone to errors because numerous TIA mimics exist and there is a shortage of evidence-based diagnostic criteria for TIAs. In this study, we applied for the first time the recently proposed explicit diagnostic criteria for transient ischemic attacks (EDCT) to a group of patients presenting to the emergency department of a large German tertiary care hospital with a suspected TIA. The aim was to determine the sensitivity and specificity of the EDCT in its clinical application. <b><i>Methods:</i></b> A total of 128 patients consecutively presenting to the emergency department of the University Hospital of Lübeck, Germany, under the suspicion of a TIA were prospectively interviewed about their clinical symptoms at the time of presentation. The diagnosis resulting from applying the EDCT was compared to the diagnosis made independently by the senior physicians performing the usual diagnostic work-up (“gold standard”), allowing calculation of sensitivity and specificity of the EDCT. <b><i>Results:</i></b> EDCT achieved a sensitivity of 96% and a specificity of 88%. When adding the additional criterion F (“the symptoms may not be better explained by another medical or mental disorder”), specificity significantly increased to 98%. <b><i>Conclusions:</i></b> The data show that the EDCT in its modified version as proposed by us are a highly useful tool for clinicians. They display a high sensitivity and specificity to accurately diagnose TIAs in patients referred to the emergency department with a suspected TIA.

Testing the validity and acceptability of the diagnostic criteria for Hoarding Disorder: a DSM-5 survey

2011 ◽  
Vol 41 (12) ◽  
pp. 2475-2484 ◽  
Author(s):  
D. Mataix-Cols ◽  
L.. Fernández de la Cruz ◽  
T. Nakao ◽  
A. Pertusa
Keyword(s):  
Diagnostic Criteria ◽  
Sensitivity And Specificity ◽  
Diagnostic Category ◽  
High Sensitivity ◽  
Obsessive Compulsive ◽  
Hoarding Disorder ◽  
Compulsive Disorder ◽  
Dsm 5 ◽  
The Individual ◽  
Development And Validation

BackgroundThe DSM-5 Obsessive-Compulsive Spectrum Sub-Workgroup is recommending the creation of a new diagnostic category named Hoarding Disorder (HD). The validity and acceptability of the proposed diagnostic criteria have yet to be formally tested.MethodObsessive-compulsive disorder/hoarding experts and random members of the American Psychiatric Association (APA) were shown eight brief clinical vignettes (four cases meeting criteria for HD, three with hoarding behaviour secondary to other mental disorders, and one with subclinical hoarding behaviour) and asked to decide the most appropriate diagnosis in each case. Participants were also asked about the perceived acceptability of the criteria and whether they supported the inclusion of HD in the main manual.ResultsAltogether, 211 experts and 48 APA members completed the survey (30% and 10% response rates, respectively). The sensitivity and specificity of the HD diagnosis and the individual criteria were high (80–90%) across various types of professionals, irrespective of their experience with hoarding cases. About 90% of participants in both samples thought the criteria would be very/somewhat acceptable for professionals and sufferers. Most experts (70%) supported the inclusion of HD in the main manual, whereas only 50% of the APA members did.ConclusionsThe proposed criteria for HD have high sensitivity and specificity. The criteria are also deemed acceptable for professionals and sufferers alike. Training of professionals and the development and validation of semi-structured diagnostic instruments should improve diagnostic accuracy even further. A field trial is now needed to confirm these encouraging findings with real patients in real clinical settings.

scholarly journals Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2019

2020 ◽  
Vol 44 ◽  
Author(s):  
Christiane Stehmann ◽  
Matteo Senesi ◽  
Shannon Sarros ◽  
Amelia McGlade ◽  
Marion Simpson ◽  
...  
Keyword(s):  
Prion Disease ◽  
Disease Surveillance ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Annual Number ◽  
Spongiform Encephalopathy ◽  
Human Prion Disease ◽  
Prospective Surveillance ◽  
Jakob Disease ◽  
Neuropathological Examination

Nationwide surveillance of Creutzfeldt-Jakob disease and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2019. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2019, 513 domestic CSF specimens were referred for 14-3-3 protein testing and 85 persons with suspected human prion disease were formally added to the national register. As of 31 December 2019, just under half (42 cases) of the 85 suspect case notifications remain classified as ‘incomplete’; 16 cases were excluded through either detailed clinical follow-up (3 cases) or neuropathological examination (13 cases); 20 cases were classified as ‘definite’ and seven as ‘probable’ prion disease. For 2019, sixty-three percent of all suspected human prion disease related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. Two possibly causal novel prion protein gene (PRNP) sequence variations were identified. Keywords: Creutzfeldt-Jakob disease, prion disease, transmissible spongiform encephalopathy, disease surveillance

scholarly journals Efficient and effective single-step screening of individual samples for SARS-CoV-2 RNA using multi-dimensional pooling and Bayesian inference

2021 ◽  
Vol 18 (179) ◽  
pp. 20210155
Author(s):  
Juliana Sobczyk ◽  
Michael T. Pyne ◽  
Adam Barker ◽  
Jeanmarie Mayer ◽  
Kimberly E. Hanson ◽  
...  
Keyword(s):  
Bayesian Inference ◽  
Sensitivity And Specificity ◽  
Disease Surveillance ◽  
High Sensitivity ◽  
Screening Strategy ◽  
Single Step ◽  
Polymerase Chain Reaction Test ◽  
Screening Protocol ◽  
The Individual ◽  
Chain Reaction Test

Rapid and widespread implementation of infectious disease surveillance is a critical component in the response to novel health threats. Molecular assays are the preferred method to detect a broad range of viral pathogens with high sensitivity and specificity. The implementation of molecular assay testing in a rapidly evolving public health emergency, such as the ongoing COVID-19 pandemic, can be hindered by resource availability or technical constraints. We present a screening strategy that is easily scaled up to support a sustained large volume of testing over long periods of time. This non-adaptive pooled-sample screening protocol employs Bayesian inference to yield a reportable outcome for each individual sample in a single testing step (no confirmation of positive results required). The proposed method is validated using clinical specimens tested using a real-time reverse transcription polymerase chain reaction test for SARS-CoV-2. This screening protocol has substantial advantages for its implementation, including higher sample throughput, faster time to results, no need to retrieve previously screened samples from storage to undergo retesting, and excellent performance of the algorithm's sensitivity and specificity compared with the individual test's metrics.

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